I. Field of the Invention
This invention relates generally to the design of cardiac pacemakers and more particularly to the timing control of a rate adaptive cardiac pacer in which the control signal for the timing circuit is derived from the ventricular ejection fraction (EF) of a beating heart and, accordingly, is responsive to metabolic demand.
II. Discussion of the Prior Art
It is well known that patients suffering from severe bradycardia or chronotropic incompetence can be helped by an implanted cardiac pacemaker designed to restore a normal, at-rest, heart rate. Typical prior art pacemakers will usually have a fixed rate or a narrow range of externally programmable rates so that they also prove efficacious in meeting metabolic demand at low levels of exercise. However, the inadequacy of such fixed rate pacers to meet metabolic demands at-rest and during exercise led to the development of a class of pacemakers referred to as "rate adaptive pacemakers". In this latter class of pacemakers, a means is provided for sensing a parameter that changes with metabolic demand and then the sensed value is used to alter the rate at which cardiac stimulating pulses are produced.
Prior art pacers assess metabolic demand through a variety of techniques or approaches. For example, such parameters as blood pH, blood temperature, QT interval, physical activity, respiration rate as well others have been disclosed in the prior art. Such pacemakers are considered as an improvement over the earlier fixed rate devices, but the majority of rate adaptive pacers now available suffer either from a lack of sensitivity to changing conditions, a lack of specificity or a lack of sufficient speed in response to changes in metabolic need. An example of a pacemaker that suffers from a lack of specificity is the Activitrax.TM. pacemaker sold by Medtronic Inc. That device uses a motion transducer to develop the control signal for modifying the pacemaker's stimulating rate. Difficulty arises in distinguishing body motion or vibration from artifacts produced by passive vibration or by motion that is not associated with an increase in metabolic demand. For example, a patient with such an activity-based sensor may be riding in a vehicle and sitting quietly, but if that vehicle should be traveling on a bumpy road, the pacing rate will inappropriately accelerate. Other relatively non-specific pacemakers are those that base the rate change on respiration parameters, such as chest impedance. The respiratory impedance signal obtained in this manner may be contaminated by motion artifacts. One example of such an artifact is the additive effect of arm movements, which unduly accelerate the rate beyond that which is dictated by the prevailing metabolic needs of the patient. In this system, to detect chest impedance, impedance plethysmography is used in which a constant current carrier signal is permanently required which detracts from the life of an implanted battery-type power source.
Temperature-controlled rate adaptive pacemakers are examples of those lacking sensitivity. This is due to the normal physiologic lag between onset and level of exercise and the point at which the body temperature rises an amount that will trigger the increase in the pacemaker's stimulating pulse rate. This slow response can also be unpredictable.
Pacemakers using the QT interval as a control parameter are also found to be quite slow in reacting to changes in metabolic demand and tend to be non-specific and somewhat erratic. Self-acceleration is common in such pacemakers, because the physiologic signal used for rate control predisposes them to positive feedback and, thus, instability.
The most accurate and physiologic systems are those that use intracardiac signals, especially those that are ventricular volume-derived, e.g., stroke volume, dV/dt, pre-ejection period. The stroke-volume controlled rate responsive pacemaker, as shown in the Olson U.S. Pat. No. 4,535,774, in the Salo U.S. Pat. No. 4,686,987 and in the Schroeppel U.S. Pat. No. 4,802,481, each suffer from a lack of specificity, since they tend to be preload-dependent. Cardiac preload can be defined as the volume of blood that returns to the heart from the circulation. Venous return is strongly influenced by cardiac cycle length (the longer the diastole, the larger the volume-per-beat), respiration, and especially postural changes, none of which truly reflect a change in metabolic demand.
Stroke volume controlled rate adaptive pacemakers are based on the relationship that normally exists between stroke volume, heart rate, cardiac output and metabolic demand. Thus, in the case of a normal healthy individual undergoing exercise, stroke volume, i.e., the amount of blood ejected in each heart beat, remains relatively constant or increases very little. The increase in cardiac output in this case is caused almost exclusively by the heart rate increase (cardiac output=stroke volume.times.heart rate). In patients with complete heart block, who are unable to undergo an increase in heart rate in proportion to increased metabolic demands, have increased cardiac output due to increased stroke volume. That is, the blood ejected with each heart beat is augmented in proportion to metabolic need. Conversely, if heart rate is artificially increased with the patient at-rest (for example, by pacing without a corresponding increase in metabolic need), there will be a decrease in stroke volume, keeping the product of the two, i.e., cardiac output, constant.
The algorithm of stroke volume-based rate adaptive pacemakers calls for an increase in pacing rate whenever there is an increase in stroke volume, and a slowing of pacing rate when stroke volume decreases. The end-point, then, is to keep stroke volume constant. Such an algorithm would be appropriate, were there are no concurrent factors, such as, postural changes, respiration, cough, etc., which strongly affect venous return to the right heart (and hence change stroke volume) without any concomitant change in metabolic need. For example, if a patient with a stroke volume-based rate adaptive pacemaker goes from the standing to the recumbent position, there will be a sudden increase in venous return to the heart, with blood from the lower extremities augmenting stroke volume. This leads to an increase in the pacing rate which is unnecessary and non-physiologic. Normal individuals react in just the opposite way. If the same subject stands up, there will be blood pooling in the lower extremities, causing a reduction in venous return to the heart. This will produce a reduction in stroke volume, which, according to the pacemaker algorithm, will effect a reduction in pacing rate, which is just the opposite of what should have happened.
It can be seen, then, that stroke volume is dependent on end-diastolic volume (EDV), a reflection of preload or venous return, and the contractile force of the heart (contractility). In the absence of metabolic-mediated contractility changes, variations of stroke volume are largely related to the so-called Frank-Starling law of the heart which states that the greater the cardiac muscle fiber stretch (produced by preload), the greater the stroke volume. Stated otherwise, the volume of blood ejected per beat will be proportional to the volume of blood contained in the ventricle at end-diastole.
One way of diminishing the influence of preload on stroke volume is by simultaneously taking into account the end-diastolic volume of the same beat. By determining the ratio of stroke volume to end-diastolic volume, it is possible to assess more accurately the contractility effect on changing volumes. This ratio is called the ejection fraction (EF), and is normally expressed as a percentage of the end-diastolic volume ejected from the ventricle. Ejection fraction is, thus, less dependent on preload and is a more accurate estimate of cardiac contractility than stroke volume alone. The same is true for a counterpart of ejection fraction, the residual fraction, also indicative of the contractile state of the heart. The residual fraction is the percentage of blood remaining in the ventricle after ejection has finished.
As is described in the prior art patent to Olive, et al., U.S. Pat. No. 4,733,667, indirect measures of the heart's contractility state may be useful signals in controlling the rate at which a rate adaptive pacemaker will operate. Pre-ejection period and rate of change of pressure or volume with respect to time are examples of indirect contractility indicators.